Effects of Non-invasive, Targeted, Neuronal Lesions on Seizures in a Mouse Model of Temporal Lobe Epilepsy.
Epilepsy surgery
Focused ultrasound
Magnetic resonance-guided
Neuronal loss
Non-invasive
Journal
Ultrasound in medicine & biology
ISSN: 1879-291X
Titre abrégé: Ultrasound Med Biol
Pays: England
ID NLM: 0410553
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
09
09
2019
revised:
13
12
2019
accepted:
13
01
2020
pubmed:
23
2
2020
medline:
13
8
2021
entrez:
22
2
2020
Statut:
ppublish
Résumé
Surgery to treat drug-resistant epilepsy can be quite effective but remains substantially underutilized. A pilot study was undertaken to test the feasibility of using a non-invasive, non-ablative, approach to produce focal neuronal loss to treat seizures in a rodent model of temporal lobe epilepsy. In this study, spontaneous, recurrent seizures were established in a mouse model of pilocarpine-induced status epilepticus. After post-status epilepticus stabilization, baseline behavioral seizures were monitored for 30 d. Non-invasive opening of the blood-brain barrier targeting the hippocampus was then produced by using magnetic resonance-guided, low-intensity focused ultrasound, through which a neurotoxin (quinolinic acid) administered intraperitoneally gained access to the brain parenchyma to produce focal neuronal loss. Behavioral seizures were then monitored for 30 d after this procedure, and brains were subsequently prepared for histologic analysis of the sites of neuronal loss. The average frequency of behavioral seizures in all animals (n = 11) was reduced by 21.2%. Histologic analyses along the longitudinal axis of the hippocampus revealed that most of the animals (n = 8) exhibited neuronal loss located primarily in the intermediate aspect of the hippocampus, while sparing the septal aspect. Two other animals with damage to the intermediate hippocampus also exhibited prominent bilateral damage to the septal aspect of the hippocampus. A final animal had negligible neuronal loss overall. Notably, the site of neuronal loss along the longitudinal axis of the hippocampus influenced seizure outcomes. Animals that did not have bilateral damage to the septal hippocampus displayed a mean decrease in seizure frequency of 27.7%, while those with bilateral damage to the septal hippocampus actually increased seizure frequency by 18.7%. The animal without neuronal loss exhibited an increase in seizure frequency of 19.6%. The findings indicate an overall decrease in seizure frequency in treated animals. And, the site of neuronal loss along the longitudinal axis of the hippocampus appears to play a key role in reducing seizure activity. These pilot data are promising, and they encourage additional and more comprehensive studies examining the effects of targeted, non-invasive, neuronal lesions for the treatment of epilepsy.
Identifiants
pubmed: 32081583
pii: S0301-5629(20)30010-7
doi: 10.1016/j.ultrasmedbio.2020.01.008
pmc: PMC8120598
mid: NIHMS1569283
pii:
doi:
Substances chimiques
Pilocarpine
01MI4Q9DI3
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1224-1234Subventions
Organisme : NCI NIH HHS
ID : R01 CA217953
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS102194
Pays : United States
Informations de copyright
Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest disclosure The authors report no conflict of interest.
Références
Seizure. 2014 Jun;23(6):475-8
pubmed: 24582999
Neurology. 2012 Sep 11;79(11):1084-93
pubmed: 22895589
Ann Neurol. 2009 Dec;66(6):858-61
pubmed: 20033983
Epilepsy Behav. 2004 Oct;5(5):696-701
pubmed: 15380121
Epilepsy Res. 1999 Apr;34(2-3):99-107
pubmed: 10210024
Epilepsia. 2013 May;54(5):840-7
pubmed: 23551133
Neurology. 2010 Aug 24;75(8):699-704
pubmed: 20733145
Synapse. 1989;3(2):154-71
pubmed: 2648633
JAMA. 1996 Aug 14;276(6):470-5
pubmed: 8691555
Brain Res. 1984 Nov 12;321(2):237-53
pubmed: 6498517
Brain Res. 1983 Jan 31;260(1):156-9
pubmed: 6297683
Ultrasound Med Biol. 2019 Jan;45(1):129-136
pubmed: 30309748
Neurobiol Dis. 2012 Jan;45(1):297-304
pubmed: 21878392
Epilepsia. 1996 Oct;37(10):1015-9
pubmed: 8822702
Eur J Neurol. 2010 Apr;17(4):619-25
pubmed: 20039934
Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4103-8
pubmed: 9108112
Ultrasound Med Biol. 2015 Feb;41(2):449-55
pubmed: 25542495
Neuron. 2010 Jan 14;65(1):7-19
pubmed: 20152109
N Engl J Med. 2001 Aug 2;345(5):311-8
pubmed: 11484687
Neurology. 2012 Apr 17;78(16):1200-6
pubmed: 22442428
Epilepsy Res. 2012 Dec;102(3):153-9
pubmed: 22721955
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13311-6
pubmed: 9371842
Neurology. 2016 Jan 5;86(1):72-8
pubmed: 26643546
Neurol Clin Pract. 2016 Oct;6(5):444-451
pubmed: 29443283
Ultrasound Med Biol. 2016 Sep;42(9):2261-9
pubmed: 27260243
Experientia. 1983 Dec 15;39(12):1408-11
pubmed: 6140182
Hippocampus. 2004;14(8):935-47
pubmed: 15390177
Brain Res. 2016 Mar 1;1634:179-186
pubmed: 26764534
Epilepsy Res Treat. 2012;2012:382095
pubmed: 22957229
Neurosurg Clin N Am. 2016 Jan;27(1):37-50
pubmed: 26615106
Epilepsia. 2006 Dec;47(12):2115-24
pubmed: 17201711
Neurology. 2003 Feb 25;60(4):538-47
pubmed: 12601090
Electroencephalogr Clin Neurophysiol. 1972 Mar;32(3):281-94
pubmed: 4110397
Epileptic Disord. 2016 Jun 1;18(2):113-21
pubmed: 27193634
Arch Neurol. 2011 Jun;68(6):725-9
pubmed: 21320984
Neurosci Lett. 1994 Feb 28;168(1-2):225-8
pubmed: 8028781
Arch Neurol. 2008 Feb;65(2):177-83
pubmed: 18268185
Lancet Neurol. 2008 Jun;7(6):525-37
pubmed: 18485316
Epilepsy Res. 2002 Apr;49(2):109-20
pubmed: 12049799
Neurosurgery. 2001 Jul;49(1):51-6; discussion 56-7
pubmed: 11440459
J Neurosci. 2013 Jul 3;33(27):11100-15
pubmed: 23825415
Neuroscience. 2017 Jun 3;352:131-143
pubmed: 28389377
Brain Res. 1986 Jul 16;378(1):169-73
pubmed: 3742197
Hippocampus. 1998;8(6):608-19
pubmed: 9882018
Behav Brain Res. 1983 Sep;9(3):315-35
pubmed: 6639740
Nat Rev Neurosci. 2014 Oct;15(10):655-69
pubmed: 25234264